The functional units of the kidney, such as the glomeruli may suffer from inflammation. An inflammatory attack in the glomeruli is termed glomerulonephritis and can be classified into subgroups such as membraneous glomerulonephritis, focal segmental glomerulosclerosis, mesangial diffuse proliferative glomerulonephritis, endocapillary or extracapillary proliferative glomerulonephritis. Using histopathological techniques these subgroups vary with respect to microscopical or immunohistochemical picture. One cause of inflammation is due to the deposition of immunoglobulin A (IgA) in glomeruli. This condition is termed IgA nephropathy (1-3), and is the most common form of glomerulonephritis in a global perspective.
Assessment of the degree of severity of glomerulonephritis is based on different investigation results. The most important findings are 1) the degree of urinary excretion of protein (proteinuria) and 2) the filtering function of the kidney, which can be assessed by serum creatinine (screatinine). Histological examination of material from kidney (renal biopsy) yields information about the type of renal damage as well as the severity of the injury. The outcome of a glomerulonephritis is variable and is dependent upon the histological and the immunohistochemical findings in a renal biopsy. Patients with IgA nephropathy having a constant proteinuria often develop renal failure and uraemia after 5 to 20 years of illness (4).
Various treatments for glomerulonephritis are known. For example substances which act on the immune system, e.g. Cyclophosphamide, Azathioprine and Cyclosporine have been used. Glucocorticoids have also been used (mainly prednisone or prednisone acetate) which may be administered orally or by venous infusion (5, 6). Unfortunately, these treatments cause severe side effects and are not particularly effective. Other suggested treatments include ACE-inhibitors (7), polyunsaturated fatty acid-preparations (8) and vitamin E (9). The treatment results for these therapies for IgA nephropathy have been quite disappointing and it has been concluded that an effective treatment against progressive IgA nephropathy is basically missing (10). For this reason, a substantial number of patients with IgA nephropathy, 20-30%, will eventually develop renal insufficiency and uraemia (1-4). The available treatment for uraemia today is dialysis or kidney transplantation. Renal transplant patients who have been transplanted because of uraemia due to glomerulonephritis frequently suffer from recurrence of glomerulonephritis in the transplant and subsequently a gradual loss of transplant function (11, 12). This is most common with patients who previously suffered from IgA nephropathy. Today there is no effective treatment against recurrence of glomerulonephritis in a transplant.
The glucocorticoids that have been used in IgA nephropathy and in other types of glomerulonephritis are characterised by a substantial gastrointestinal absorption after oral administration, aiming to exert a direct effect on circulating leukocytes and cells that have infiltrated the kidney or the renal transplant, thus having a systemic effect. Such a systemic effect is also achieved if glucocorticoids are administered as an intravenous infusion. Systemic administration of glucocorticoids may have influenced the outcome of IgA nephropathy in some cases.